Outcome After Systemic Thrombolysis Is Predicted by Age and Stroke

Neurology International 2012; volume 4:e9

Outcome after systemic rological deficit at stroke admission, and a proximal MCA occlusion. Half of the surviving Correspondence: Rüdiger J. Seitz, Department of thrombolysis is predicted by patients improved to no or minimal impair- Neurology, University Hospital Düsseldorf age and stroke severity: an ment. Moorenstrasse 5, 40225 Düsseldorf, Germany. open label experience with Tel. +49.211.8118974 - Fax: +49.211.8118485. recombinant tissue E-mail: [email protected] plasminogen activator and Introduction Key words: brain infarct, stroke, thrombolysis, tirofiban tirofiban, impairment. Systemic thrombolysis with the recombi- Funding: the study was supported by the Rüdiger J. Seitz,1,2,3 Judith Sukiennik,1 nant tissue plasminogen activator (rtPA) is the Competence Net Stroke of the BMBF. Mario Siebler1,4 only approved treatment of acute ischemic stroke. It aims at rapid recanalization of the Conflict of interests: the authors report no poten- 1Department of Neurology, University occluded cerebral artery affording neurological tial conflict of interests. Hospital Düsseldorf, 2Biomedical recovery.1 In recent years it was shown that Research Centre, Heinrich-Heine- early recanalization results in better neurolog- Received for publication: 28 September 2011. University Düsseldorf, Germany; ical outcome and less lesion growth than lack- Revision received: 11 June 2012. 3 Accepted for publication: 30 July 2012. Florey Neuroscience Institutes, ing recanalization.2-4 However, the severity of Melbourne, Australia; 4Department the ischemic attack prior to thrombolytic treat- This work is licensed under a Creative Commons of Neurology, Mediclin Fachklinik Rhein ment and a poor status of arterial collaterals Attribution NonCommercial 3.0 License (CC BY- Ruhr, Essen, Germany have been described to predict a poor recov- NC 3.0). ery.5,6 On average, thrombolysis has been found to enhance the proportion of patients ©Copyright R.J. Seitz et al., 2012 Licensee PAGEPress, Italy with a favorable outcome after ischemic stroke Neurology International 2012; 4:e9 Abstract and to downsize the proportion of patients with doi:10.4081/ni.2012.e9 severe neurological deficits.7-9 In fact, a large Stroke patients can recover upon intra- recent meta-analysis of different thrombolysis venous thrombolysis but remain impaired in studies revealed that the application of through 2007. We investigated four questions: lacking recanalization. We sought to investi- alteplase rendered some 42 percent of patients i) what is the proportion of patients who bene- gate the clinical effect of systemic thrombolysis with an excellent outcome [modified Rankin fit from this treatment? ii) what is the propor- with an intravenous bolus of 20 mg recombi- Scale (mRS) of 0 and 1] on day 90 as compared tion of patients who do not benefit from this nant tissue plasminogen activator (rtPA) and with 30 percent of patients receiving placebo.10 treatment? iii) what is the proportion of an infusion of body-weight adjusted tirofiban Prompted by the results of platelet receptor patients who expire after this stroke treat- for 48 hours in acute stroke. This prospective, inhibition in the management of patients with ment? iv) what are predictors for poor or good open label study, included 192 patients (68±13 acute myocardial ischemia we have introduced recovery? years, 50% males) treated between 1 January a regime for systemic thrombolysis composed 2005 and 31 December 2007. The neurological of an intravenous bolus of low dose rtPA in deficit was assessed with the National combination with a subsequent infusion of the Institutes of Health stroke scale (NIHSS). nonpeptide GPIIb/IIIa platelet receptor antago- Materials and Methods Follow-up was performed using a telephone nist tirofiban.11,12 The rational for a low dose of interview of modified Rankin Scale (mRS) and rtPA was to avoid intra- and extracranial hem- Subjects Barthel index. The site of cerebral artery occlu- orrhage, since symptomatic and fatal hemor- All patients who were treated with systemic sion was determined by computed tomography rhages are a severe complication of a high thrombolysis on the Stroke Unit of our institu- or magnetic resonance angiography. Data were dose of rtPA.13 Further, GPIIb/IIIa receptor tion between 1 January 2005 and 31 December analyzed by descriptive statistics and multiple antagonists selectively inhibit the platelet regression analyses. Eighty-one percent of the integrin IIbIII fibrinogen receptor and there- 2007 were included. Criteria for inclusion into patients had an infarct in the middle cerebral by inhibit platelet aggregation.14,15 Since rtPA this study were: artery (MCA) territory and were severely affect- is known to induce a hypercoagulation follow- - an acute ischemic brain infarct, ed with a median NIHSS of 10. During treat- ing thrombolysis,16 tirofiban was expected to - documentation of a causal cerebral artery ment on the Stroke Unit the patients improved antagonize the hypercoagulation following occlusion before thrombolysis using com- (P<0.0001) except for patients who deceased rtPA administration and thereby help to main- puted tomographic angiography (CTA) or due to malignant infarction (n=10) or cerebral tain the cerebral blood vessels patent after magnetic resonance angiography (MRA), haemorrhage (n=6); 18 percent deceased with- thrombolysis. Likewise, it might help to disag- - systemic thrombolysis with rtPA and in 100 days which was predicted by older age gregate secondary thrombi resulting from the tirofiban, (76 + 10 years, P<0.05) and more severe affec- large thrombus in the initially occluded cere- - clinical evaluation on admission and at dis- tion on admission (P<0.0001). Also, these bral artery. We have shown previously that the charge from the Stroke Unit using the patients more frequently had atrial fibrillation combined use of low dose rtPA and tirofiban is stroke scale of the National Institutes of (P<0.03) than the surviving patients. The sur- safe and effective.12,17 Thus, we used this Health (NIHSS), the mRS and Barthel index viving patients had more frequently distal MCA treatment as first line regime. (BI),18-21 occlusions and improved further (P<0.0001). In this prospective mono-center, non-ran- - follow-up telephone questionnaire of the BI At follow-up 48% of the patients had a mRS of 0 domized study we analyzed the clinical data of and mRS, which was performed after at least and 1. Similarly to intravenous thrombolysis the consecutive patients treated with a low 130 days (median 487 days, range 131-1056 with body-weight adjusted rtPA, poor prognosis bolus of rtPA and a subsequent infusion of days). was predicted by higher age, more severe neu- tirofiban in our hospital in the years 2005 Patients were subjected either to computed

[Neurology International 2012; 4:e9] [page 35] Article tomography including CTA or multiparametric 0.001). Twenty-three patients died with 6 magnetic resonance imaging including a MRA patients due to an intracranial haemorrhage Discussion depending on availability prior to thrombolysis. (3.1%) and 10 patients suffering malignant Thrombolysis was performed in each patient brain infarction. After discharge eleven further This study revealed that the combined use with an intravenous bolus of 20 mg rtPA with- patients deceased such that 34 patients (18%) of an intravenous bolus of low dose rtPA and a in 3 h after stroke onset followed immediately deceased within 100 days after stroke (Figure subsequent body-weight adjusted infusion of by an intravenous infusion of tirofiban.12,17 2). Death was predicted by older age (76±10 tirofiban had an optimal outcome (mRS of 0 Tirofiban was given in a body-weight adjusted years, P<0.05) and a more severe affection and 1) at follow-up in about 48 percent of our dosage starting with a bolus of 0.4 mg/ kg body (mRS 5, P<0.0001). Also, the patients more fre- patients. In comparison to the large clinical tri- weight/min for 30 min followed by continuous quently had atrial fibrillation (P<0.03) than the als of systemic application of rtPA this was infusion of 0.1 mg/ kg body weight/min for 48 h. surviving patients. But none of the other vascu- clearly better than in the placebo group and In addition, patients were treated according to lar risk factors was predicting or different similar to the thrombolysis group.10 Note, that their individual requirements. The treatment between the deceased or surviving patients the patients in this study had a median NIHSS procedure and the study were approved by the (Table 1). The surviving patients improved fur- at treatment onset of 10 being as severely Ethics Committee of the Heinrich-Heine- ther (P<0.0001) leaving 48% of study cohort affected as the patients in the ECASS 3 study.1 University Düsseldorf, Germany. The patients with a mRS of 0 and 1 at follow-up, while 18 % Importantly, the patients who benefitted from gave informed consent. of the patients were still severely affected hav- our treatment regime were younger and less ing a mRS of 4 or 5 (Figure 3). severely affected at stroke onset than those Statistical analysis Statistical analysis was done using SPSS 10.1 for Windows (release 2005). Group comparisons were done using the two-tailed t-test. Evaluation Table 1. Characteristics of the 192 patients. of the neurological deficit and the impairment was assessed with the non-parametric Mann- Age (years ± SD) 70±13 Whitney test. Group comparison of the abnor- Male/Female (n) 95/97 malities in the cerebral arterial circulation was NIHSS, admission (median, range) 10 (2-27) performed with the distribution free Wilcoxon’s BI, admission (median, range) 30 (0-100) rank test. Multiple regression analyses were per- mRS, admission (median, range) 4 (0-5) formed to single out the variables that account- ed for the effect of thrombolysis. NIHSS, discharge (median, range) 3 (0-23)* BI, at discharge (median, range) 80 (0-100)* mRS, at discharge (median, range) 3 (0-6)* Arterial hypertension (%) 85 Results Diabetes mellitus (%) 20 Atrial fibrillation (%) 36 Of 2241 patients treated on the Stroke Unit Coronary artery disease (%) 26 of this institution in 2005 through 2007, 252 Current smoking (%) 22 patients (11%) were treated with systemic *Significant change from admission to discharge (P<0.0001, Wilcoxon rank test). NIHSS, Stroke Scale of the National Institute of Health; thrombolysis using intravenous rtPA and mRS, modified Rankin Scale; BI, Barthel index. tirofiban. Fifteen patients were subjected to body weight adjusted rtPA or received a catheter intervention due to a stroke in the vertebrobasilar territory. The 192 patients (70±13 years, 50 percent males) matching the inclusion criteria of this study were severely impaired at stroke onset having a median NIHSS of 10 (range 2-27). 81% of the patients had a middle cerebral artery (MCA) territory infarct. There were only few patients with a tandem occlusion of the internal carotid artery (ICA) and the MCA. On average the patients improved by 7 points on the NIHSS (P<0.0001) until discharge from the Stroke Unit (Table 1). The profound improvement was also apparent in the mRS, and BI (Table 1). The majority of the patients with a tandem occlusion of the ICA and MCA deceased. In contrast, the more peripheral the MCA occlusions occurred, the more patients survived (Figure 1). There was no difference among the subgroups concerning age, gender or vascular risk factors, apart from atrial fibrillation being more frequent in tandem occlusions of the ICA and MCA or at the Figure 1. Influence of the location of the occlusion of the middle cerebral artery on the rate of survival. The numbers in each column indicate the number of patients. bifurcation as compared to a MCA-branch (P<

[page 36] [Neurology International 2012; 4:e9] Article who remained severely impaired or deceased. er cardioembolic thrombi would occlude larger In accordance with other recent studies we This was the case both at discharge from the more proximal arteries including the distal ICA found that the rate of survival was better the Stroke Unit and for follow-up up to 100 days and that the thrombi may be more resistant to more distal the occlusion of the MCA was.34-37 after stroke. These data accord well with recent thrombolysis in older than in younger patients. Similar results were obtained concerning the reports about intravenous thrombolysis with Both factors would prevent rapid recanaliza- neurological disability and recovery.17,38 Most 0.9 mg rtPA per kilogram body weight in the tion, early reperfusion and neurological recov- likely, this was due to smaller infarcts in more Safe Implementation of Thrombolysis in ery.1-4 Since rtPA is beneficial also in the elder- distal cerebral artery occlusions that have been Stroke Monitoring Study,22 the Virtual ly,32,33 it should not be withheld from them in found to exhibit a better recanalization rate.34-39 International Stroke Trial Archive,23 and the acute stroke. But oral anticoagulation because It is tempting to speculate that mechanical Diffusion and Perfusion Imaging Evaluation of absolute arrhythmia related to atrial fibrilla- devices may be employed in patients with prox- for Understanding Stroke Evolution.24 These tion is of even greater importance. imal MCA occlusions. The benefit of tirofiban and our data accord with the notion that age and initial NIHSS impact on clinical outcome independent of treatment. Our rational for the combined use of low- dose rtPA and a subsequent infusion of tirofiban was our attempt to minimize the risk of cerebral hemorrhage on one hand and to counteract arterial reocclusion after stroke and thrombolysis.16 Thrombus formation involves the aggregation of activated platelets and the bridging between platelets by fibrinogen via the reconfigured GPIIb/IIIa platelet receptor.25,26 The GPIIb/IIIa receptor is a proto- typic integrin which is exclusively expressed on the membranes of platelets and megakary- ocytes. In experimental stroke models, GPIIb/IIIa antagonists given as only drug or in combination with rtPA have been shown to be safe and effective, since the treated animals had reduced infarct volumes.27,28 Clinical studies suggest that tirofiban can disintegrate acute thrombi in the large internal carotid artery and suppress microemboli as detected with transcranial Doppler sonography.29 Moreover, in small prospective series we were able to show that a low-dose bolus of 20 mg Figure 2. Distribution of dead patients following acute stroke. The majority of patients rtPA and body-weight adjusted infusion of expired within the first 100 days. Note that 23 patients already died on the Stroke Unit (open column). tirofiban resulted in a profound clinical recovery along with recanalization and a decrease in infarct volume.12,17 Similarly, the monoclonocal antibody abciximab that also targets the platelet GPIIb/IIIa receptors was shown to be effective when combined with rtPA in the interventional treatment of vertebrobasilar stroke.30 In contrast, abciximab was found to result in an exaggeration of fatal hemorrhages and not to improve outcome in stroke of the anterior circulation.31 Since the non-peptide tirofiban was found to be safe in stroke,18 it is possible that the monoclonal antibody abciximab blocked the GPIIb/IIIa receptors of all cir- culating platelets irreversibly precipitating hemorrhagic complications. In our patients atrial fibrillation was more frequent in the more severely affected patients with more proximal MCA occlusions than in the less severely affected patients. These data highlight the impact of cardioembolic stroke for disability and dependence particularly in the elderly. In contrast, the vascular risk factors were not predictive for poor outcome or Figure 3. Neurological impairment of the 192 patients as assessed with the modified discriminating between good recovery and Rankin Scale on admission before thrombolysis (A) and at follow up (F). Note that half of the patients had no only or little impairment at follow up.20 poor recovery or death. It is possible that larg-

[Neurology International 2012; 4:e9] [page 37] Article in such a situation is that it can be combined tic implications. Neurology 2007;68:39-44. serves microvascular patency in experi- with local thrombolysis enhancing its effect 4. Davis S, Donnan G, Parsons M, et al. mental acute focal cerebral ischemia. beyond the narrow time window of thromboly- Effects of alteplase beyond 3 h after stroke Stroke 2000;31:1402-9. sis. Thus, it may be of interest in the context of in the Echoplanar Imaging Thrombolytic 16. Saqquar M, Molina CA, Salem A, et al. interventional approaches for the treatment of Evaluation Trial (EPITHET) a placebo-con- Clinical deterioration after intravenous acute stroke. trolled randomised trial. Lancet Neurol recombinant tissue plasminogen activator The rate of fatal hemorrhage in our study 2008;7:299-309. treatment: a multicenter transcranial was in the range of thrombolysis with 0.9 mg 5. Seitz RJ, Meisel S, Weller P, et al. The initial Doppler study. Stroke 2007;38:69-74. rtPA per kilogram body weight.34-42 This ischemic event: PWI and ADC for stroke 17. Seitz RJ, Hamzavi M, Junghans U, et al. accords with our recent observation that evolution. Radiology 2005;237:1020-8. Thrombolysis with recombinant tissue tirofiban does not increase the bleeding rate in 6. Bang OY, Saver JL, Buck BH, et al. Impact plasminogen activator and tirofiban in acute stroke.18 It should be noted that in that of collateral flow on tissue fate in acute stroke. Preliminary observations. Stroke former study tirofiban was administered as a ischaemic stroke. J Neurol Neurosurg 2003;34:1932-5. single drug or in addition to aspirin, while in Psychiatry 2008;79:625-9. 18. Siebler M, Hennerici MG, Schneider D, et this study tirofiban was combined with rtPA 7. Kidwell CS, Saver JL, Mattiello J, et al. al. Safety of tirofiban in acute ischemic even in patients receiving clopidogrel hydro- Thrombolytic reversal of acute human stroke. The SaTIS trial. Stroke 2011;42: gensulfate prior to their present stroke. cerebral ischemic injury shown by diffu- 2388-92. sion/perfusion magnetic resonance imag- 19. Brott T, Adams HP Jr, Olinger CP, et al. ing. Ann Neurol 2000;47:462-9. Measurements of acute cerebral infarc- 8. Rother J, Schellinger PD, Gass A, et al. tionpp.a clinical examination scale. Stroke Conclusions Effect of intravenous thrombolysis on MRI 1989;20:864-70. parameters and functional outcome in 20. van Swieten JC, Koudstaal PJ, Visser MC, Here, we have shown that the combined use acute stroke <6 hours. Stroke 2002;33: et al. Interobserver agreement for the of an intravenous bolus of 20 mg rtPA and a 2438-45. assessment of handicap in stroke patients. subsequent body-weight adjusted infusion of 9. Albers GW, Thijs VN, Wechsler L, et al. Stroke 1998;19:604-7. tirofiban had an efficacy and safety similarly to Magnetic resonance imaging profiles pre- 21. Mahoney F, Barthel D. Functional evalua- systemic thrombolysis with body-weight dict clinical response to early reperfusion. tion. The Barthel index. Md State Med J adjusted rtPA. Our study, however, has limita- The diffusion and perfusion imaging eval- 1965;14:61-5. tions. First, we did not perform a direct com- uation for understanding stroke evolution 22. Wahlgren N, Ahmed N, Eriksson N, et al. parison with the standard thrombolytic treat- (DEFUSE) study. Ann Neurol 2006;60:508- Multrivariable analysis of outcome predic- ment with body-weight adjusted rtPA. As evi- 17. tors and adjustment of main outcome dent from this study and calculated from the 10. Lees KR, Bluhmki E, von Kummer R, et al. results to baseline data profile in random- known effect size, a double-blind, randomized, Time to treatment with intravenous ized controlled trials: safe implementation multi-center trial would require at least 5000 alteplase and outcome in stroke: an updat- of thrombolysis in stroke-monitoring study patients per treatment arm. Also, since rtPA ed pooled analysis of ECASS, ATLANTIS, (SITS-MOST). Stroke 2008;39:3316-22. has been approved as standard care for acute NINDS, and EPITHET trials. Lancet 2010; 23. Hallevi H, Albright KC, Martin-Schild SB, stroke, a placebo control group was ethically 375:1695-703. et al. Recovery after ischemic stroke. not acceptable. Second, we did not asses the 11. The platelet receptor inhibition in Criteria for good outcome by level of dis- rate of early recanalization in these patients. ischemic syndrome management in ability at day 7. Cerebrovasc Dis 2009;28: This will be the topic of a subsequent study. patients limited by unstable signs and 341-8. Third, since it is difficult to follow-up patients symptoms (PRISM-PLUS) study investiga- 24. Vora NA, Shook SJ, Schumacher HC, et al. for face-to-face interviews, we chose to per- tors. Inhibition of the platelet glycoprotein A 5-item scale to predict stroke outcome form the follow-up study using telephone inter- IIb/IIIa receptor with tirofiban in unstable after cortical middle cerebral artery terri- views. It has been found previously that both angina and non-Q-wave myocardial infarc- tory infarction: validation from results of the BI and mRS can be used reliably in this tion. N Engl J Med 1998;338:1488-97 the diffusion and perfusion imaging eval- way.43,44 Fourth, we did not monitor depression 12. Seitz RJ, Siebler M. Platelet GPIIb/IIIa uation for understanding stroke evolution or dementia that both have been reported to receptor antagonists in human ischemic (DEFUSE) study. Stroke 2011;42:645-9. affect post-stroke recovery and death.45 brain disease. Curr Vasc Pharmacol 2008; 25. Kulkarni S, Dopheide SM, Yap CL, et al. A 6:29-36. revised model of platelet aggregation. J 13. Hacke W, Kaste M, Fieschi C, et al. Clin Invest 2000;105:783-91. Randomised double-blind placebo-con- 26. Schwarz M, Meade G, Stoll P, et al. References trolled trial of thrombolytic therapy with Conformation-specific blockade of the intravenous alteplase in acute ischaemic integrin GPIIb/IIIa: a novel antiplatelet 1. Hacke W, Kaste M, Bluhmki E, et al. stroke (ECASS II). Second European- strategy that selectively targets activated Thrombolysis with alteplase 3 to 4.5 hours Australasian Acute Stroke Study platelets. Circ Res 2006;99:25-33. after acute ischemic stroke. N Engl J Med Investigators. Lancet 1998;352:1245-51. 27. Shuaib A, Yang Y, Nakada MT, et al. 2008;359:1317-29. 14. Choudhri TF, Hoh BL, Zerwes HG, et al. Glycoprotein IIb/IIIa antagonist, murine 2. Delgado-Mederos R, Rovira A, Alvarez- Reduced microvascular thrombosis and 7E3 F(ab’)2, and tissue plasminogen acti- Sabín J, et al. Speed of tPA-induced clot improved outcome in acute murine stroke vator in focal ischemiapp.evaluation of lysis predicts DWI lesion evolution in by inhibiting GP IIb/IIIa receptor-mediated efficacy and risk of hemorrhage with com- acute stroke. Stroke 2007;38:955-60. platelet aggregation. J Clin Invest 1998: bination therapy. J Cereb Blood Flow 3. Zangerle A, Kiechl S, Spiegel M, et al. 102;1301-10. Metab 2002;22:215-22. Recanalization after thrombolysis in 15. Abumiya T, Fitridge R, Mazur C, et al. 28. Meada M, Moriguchi A, Mihara K, et al. stroke patientsp. Predictors and prognos- Integrin alpha(IIb) beta(3) inhibitor pre- FK419, a nonpeptide platelet glycoprotein

[page 38] [Neurology International 2012; 4:e9] Article

IIb/IIIa antagonist, ameliorates brain 33. Ford GA, Ahmed N, Azevedo E, et al. dicted by the initial DWI lesion. infarction associated with thrombotic Intravenous alteplase for stroke in those Cerebrovasc Dis 2011;31:580-7. focal cerebral ischemia in monkeys: com- older than 80 years old. Stroke 2010;41: 40. Blinzler C, Breuer L, Huttner HB, et al. parison with tissue plasminogen activator. 2568-74. Characteristics and outcome of patients J Cereb Blood Flow Metab 2005;25:108-18. 34. Kim YS, Garami Z, Mikulik R, et al. Early with early complete neurological recovery 29. Junghans U, Siebler M. Cerebral microem- recanalization rates and clinical outcomes after thrombolysis for acute ischemic bolism is blocked by tirofiban, a selective in patients with tandem internal stroke. Cerebrovasc Dis 2010;31:185-90. nonpeptide platelet glycoprotein IIb/IIIa carotid/middle cerebral artery occlusion 41. Fonarow G, Reeves M, Zhao X, et al. Get receptor antagonist. Circulation 2003;107: and isololated middle cerebral artery wth the guidelines-stroke steering com- 2717-21. occlusion. Stroke 2005;36:869-71. mittee and investigators. Age-related dif- 30. Eckert B, Koch C, Thomalla G, et al. 35. Wunderlich MT, Goertler M, Postert T, et al. ferences in characteristics, performance Aggressive therapy with intravenous Recanalization after intravenous throm- measures, treatment trends, and out- abciximab and intra-arterial rtPA and bolysis: does a recanalization time window comes in patients with ischemic stroke. additional PTA/stenting improves clinical exist? Neurology 2007;68:1364-8. Circulation 2010;121:879-91. outcome in acute vertebrobasilar occlu- 36. Fiehler J, Knudson K, Thomalla G, et al. 42. Arnold M, Halpern M, Meier N, et al. Age- sion: combined local fibrinolysis and intra- Vascular occlusion sites determine differ- dependent differences in demographics, venous abciximab in acute vertebrobasilar ences in lesion growth from early apparent risk factors, co-morbidity, etiology, man- stroke treatment (FAST): results of a mul- diffusion coefficient lesion to final infarct. agement, and clinical outcome of acute ticenter study. Stroke 2005;36:1160-5. Am J Neuroradiol 2005;26:1056-61. ischemic stroke. J Neurol 2008;255:1503-7. 31. Adams HP Jr, Effron MB, Torner J, et al. 37. Derex L, Hermier M, Adeleine P, et al. 43. Korner-Bitensky N, Wodd-Dauphinee S. Emergency administration of abciximab Influence of the site of arterial occlusion Barthel index information elicited over the for treatment of patients with acute on multiple baseline hemodynamic MRI telepone. Is ist reliable? Amer J Phys Med ischemic stroke: results of an internation- parameters and post-thrombolytic recanal- Rehabil 1995;74:9-18. al phase III trialpp.abciximab in emer- ization in acute stroke. Neuroradiology 44. Janssen PM, Visser NA, Dorhout Mees SM, gency treatment of stroke trial (AbESTT- 2004;46:883-7. et al. Comparison of telephone and face-to- II). Stroke 2008;39:87-99. 38. Hacke W, Donnan G, Fieschi C, et al. face assessment of the modified Rankin 32. Mishra NK, Ahmed N, Andersen G, et al. Association of outcome with early stroke Scale. Cerebrovasc Dis 2010;29:137-9. Thrombolysis in very elderly people: con- treatmentpp.pooled analysis of ATLANTIS, 45. Pendlebury S, Rothwell P. Prevalence, inci- trolled comparison of SITS international ECASS, and NINDS rt-PA stroke trials. dence, and factors associated with pre- stroke thrombolysis registry and virtual Lancet 2004;363:768-74. stroke and post-stroke dementiapp.a sys- international stroke trials archive. Br Med 39. Seitz RJ, Oberstrass H, Ringelstein A, et al. tematic review and meta-analysis. Lancet J 2010;341:c6046. Failed recovery from thrombolysis is pre- Neurol 2009;8:1006-18.

[Neurology International 2012; 4:e9] [page 39] Copyright of Neurology International is the property of PAGEPress and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.